ß3-adrenergic agonist counters oxidative stress and Na+-K+ pump inhibitory S-glutathionylation of placental cells: Implications for preeclampsia.

Oxidative stress from placental ischemia/reperfusion and hypoxia/reoxygenation (H/R) in preeclampsia is accompanied by Na+-K+ pump inhibition and S-glutathionylation of its ß1 subunit (GSS-ß1), a modification that inhibits the pump. ß3-adrenergic receptor (ß3-AR) agonists can reverse GSS-ß1. We examined effects of the agonist CL316,243 on GSS-ß1 and sources of H/R-induced oxidative stress in immortalized first trimester human trophoblast (HTR-8/SVneo) and freshly isolated placental explants from normal term pregnancies. H/R increased GSS-ß1 and, reflecting compromised α1/ß1 subunit interaction, it reduced α1/ß1 pump subunit co-immunoprecipitation. H/R increased p47phox/p22phox NADPH oxidase subunit co-immunoprecipitation reflecting membrane translocation of cytosolic p47phox that is needed to activate NADPH oxidase. Fluorescence of O2•--sensitive dihydroethidium increased in parallel. H/R increased S-glutathionylation of endothelial nitric oxide synthase (GSS-eNOS) that uncouples NO synthesis towards synthesis of O2•- and reduced trophoblast migration. Oxidative stress induced by tumor necrosis factor α (TNF-α) increased soluble fms-like tyrosine kinase receptor 1 (sFlt-1) trophoblast release, a marker of preeclampsia, and reduced trophoblast integration into endothelial cellular networks. CL316,243 eliminated H/R-induced GSS-ß1 and decreases of α1/ß1 subunit coimmunoprecipitation, eliminated NADPH oxidase activation and increases in GSS-eNOS, restored trophoblast migration, eliminated increased sFlt-1 release and restored trophoblast integration in endothelial cell networks. H/R induced GSS-ß1, α1/ß1 subunit co-immunoprecipitation and NADPH oxidase activation of placental explants reflected effects of H/R for trophoblasts and CL316,243 eliminated these changes. We conclude a ß3-AR agonist counters key pathophysiological features of preeclampsia in vitro. ß3 agonists already in human use for another purpose are potential candidates for re-purposing to treat preeclampsia.

Automated coordinate system estimation: A preliminary step toward computer-assisted radial head arthroplasty planning.

The success of radial head arthroplasty (RHA) relies on the design of the implant and precision of the surgical technique, with preoperative planning potentially playing a crucial role. The accurate establishment of a patient-specific anatomical coordinate system (ACS) is essential for this planning process. This study tested the hypothesis that an innovative automated method would be an accurate, reliable, and efficient framework to determine the ACS of the proximal radius, which would be a step toward improving the precision of RHA planning. We used advanced computational techniques to analyze 50 forearm CT scans, comparing the accuracy, reproducibility, reliability, and efficiency of the automated method with manually derived ACS using expert observers as benchmarks. The results showed that the automated approach was more accurate in identifying anatomical landmarks, with smaller mean distance discrepancies (0.6 mm) than manual observers (1 mm). Its reproducibility was also superior, with narrower reproducibility limits, particularly for ulnar notch landmarks (0.6 to 0.8 mm compared to manual selection 1.2 to 1.4 mm) (p = .01). In addition, the limits of agreement and the mean absolute rotational and translational differences of the axes were narrower for the automated method, which also reduced the construction time to an average of 46 s compared to 150 s manually (p < .001). These findings suggest that the automated method has the potential to enhance the accuracy and efficiency of preoperative and postoperative computer-assisted procedures for RHA. Further research is needed to fully understand the utility of this automated system for enhancing RHA computer-assisted surgical planning.

Midface Skeletal Sexual Dimorphism: Lessons Learned from Advanced Three-dimensional Imaging in the White Population.

Background: Facial shape is significantly influenced by the underlying facial bony skeleton. Sexual dimorphisms in these structures are crucial for craniofacial, aesthetic, and gender-affirming surgery. Previous studies have examined the orbits and upper face, but less is known about the midface. This study aimed to elucidate the sexual dimorphism in the midface region, focusing on the maxilla and zygomatic bones. Methods: A retrospective review was conducted using facial computed tomography scans from 101 White patients aged 20-79 years, using Materialise Mimics and 3-Matics for segmentation and 3D reconstruction. Measurements and statistical shape modeling of the midfacial skeleton were performed. Results: Our results show a distinct sexual dimorphism in the midfacial skeletal structure across all age groups. Women typically had a narrower bizygomatic width by 1.5 mm (P = 0.04), a shallower maxillary depth by 1.6 mm (P < 0.01), and a midfacial vertical height that was 4 mm shorter than that of men (P = 0.018). In contrast, men exhibited a greater distance between the frontozygomatic sutures by 5.4 mm (P < 0.01), a 3-mm greater interorbitale distance (P < 0.01), and a 2.1-mm wider infraorbital foramina distance (P = 0.007). There were no significant differences in the pyriform and maxillary angles (P = 0.15 and P = 0.52, respectively). Conclusions: Our analysis of midfacial skeletal anatomy revealed sexual dimorphism differences. Men exhibited more pronounced facial features than women, with a broader horizontal midfacial skeleton, a longer midfacial vertical height, and greater maxillary depths compared with women.

Hyoid Position and Aging: A Comprehensive Analysis Using AI-assisted Segmentation of 282 Computed Tomography Scans.

Background: With neck, aging the cervicomental angle becomes obtuse and may be influenced by hyoid bone aging. An understanding of hyoid position changes with aging will further our understanding of its role in neck contour changes. Methods: A 3D volumetric reconstruction of 282 neck computed tomography scans was performed. The cohort was categorized into three groups based on age: 20 years or older and younger than 40 years, 40 years or older and younger than 60 years, and 60 years or older and younger than 80 years. The vertical and horizontal hyoid distances in relation to the mandible were calculated for each patient. Results: A total of 282 patients (153 women, 129 men) were included in the cohort. The age groups were evenly distributed in men and women. Mean hyoid vertical and horizontal distances differed between women and men in all age groups. There was a significant difference in the hyoid vertical distance between 20-39 years old to 40-59 years old in men (P < 0.01), and 20-39 years old to 60-79 years old in both genders (women P = 0.005, men P < 0.01). Hyoid horizontal distance was not affected by age and sex (age and sex: P > 0.05), but rather by body mass index (BMI). Every 5 BMI points corresponded to a forward movement of 2 mm. Conclusions: As individuals age, the hyoid bone descends in both sexes, and an increase in BMI is associated with forward movement. Additional studies are needed to assess the correlation of the hyoid position between upright and supine positions.

The Posterior Triangle and Posterior Muscles of the Neck in 3-Dimensions: Creating a Digital Anatomic Model Using Peer-Reviewed Literature, Radiographic Imaging, and an Experienced Medical Illustrator.

INTRODUCTION: The posterior cervical triangle houses an important nodal basin in the spread of several cancers in the head and neck, particularly cutaneous malignancies of the scalp. A safe and effective Level V neck dissection necessitates thorough understanding of the neurovascular structures housed within the region. Conventional 2D anatomical representations offer insights into the named structures, but fall short in illustrating the spatial relationships crucial in surgery. Here, we aim to develop an anatomically-precise 3D virtual model of the posterior cervical triangle and its constituent structures. METHODS: Musculature and neurovasculature were segmented from the computerized tomography (CT) angiogram of a healthy 29-year-old female. Literature review of cadaveric studies was performed to identify the most common variants, relevant surgical relationships, and usual dimensions of structures contained in the model. Structures unable to be visualized on imaging were created de novo using data obtained in the literature review. A medical illustrator then used this data to develop a 3D anatomical model using ZBrush. RESULTS: The musculature (sternocleidomastoid, trapezius, omohyoid, scalenes, erector spinae, and transversospinalis muscles) and neurovasculature (spinal accessory nerve, phrenic nerve, vertebral artery, subclavian artery, and brachial plexus) were characterized through literature review. Musculature and vasculature were segmented from CT angiography while neural structures were created de novo. Both radiographic and anatomic data were used to inform the creation of a 3D model, which will be uploaded to an online database for open access viewing. CONCLUSIONS: A dynamic understanding of the spatial relationships existing among structures housed within the posterior triangle of the neck is imperative when operating in the region. The development of an accurate 3D anatomical model of such structures based upon predominant variants found in the literature will supplement the education of practicing and aspiring head and neck surgeons.

Combined Endoscopic Endonasal and Contralateral Transmaxillary Approach for Resection of an Anterior Petrous Chondrosarcoma: A 2-dimensional Operative Video.

The contralateral transmaxillary corridor improves access to anterior petrous apex lesions back to the level of the internal auditory canal without the need to mobilize the paraclival internal carotid artery. In this Video 1, we present the case of 31-year-old female patient who presented with new left abducens palsy during pregnancy. Imaging revealed a heterogeneous enhancing extradural mass within the left petrous apex region extending posterior to the horizontal segment of the petrous internal carotid artery, consistent with chondrosarcoma. Chondrosarcomas are the second most common osseous malignancy but only consist of 0.2% of all intracranial tumors.1,2 They are thought to derive from persistent cartilaginous rests retained after endochondral ossification.3 Given that surgery is a mainstay of treatment,4-6 a combined endoscopic endonasal and contralateral transmaxillary approach was selected to achieve maximal resection. The patient consented to the procedure. A complete resection of the mass was performed with pathology demonstrating a grade 2 chondrosarcoma. The patient tolerated the procedure without any complications, the left abducens palsy resolved in follow-up by 3 weeks, and a multidisciplinary tumor board recommended postoperative observation without adjuvant therapy.7 An endoscopic endonasal and contralateral transmaxillary approach is a feasible option for petrous apex lesions such as chondrosarcoma.

Mandibular Gender Dimorphism: The Utility of Artificial Intelligence and Statistical Shape Modeling in Skeletal Facial Analysis.

BACKGROUND: In gender-affirming surgery, facial skeletal dimorphism is an important topic for every craniofacial surgeon. Few cephalometric studies have assessed this topic; however, they fall short to provide skeletal contour insights that direct surgical planning. Herein, we propose statistical shape modeling (SSM) as a novel tool for investigating mandibular dimorphism for young white individuals. METHODS: A single-center, retrospective study was performed using computed tomography (CT) scans of white individuals, aged 20 to 39 years old. AI-assisted, three-dimensional (3D) mandibles were reconstructed in Materialise Mimics v25.0. We used SSM to generate average 3D models for both genders. Relevant manual anthropometric measurements were taken for the SSMs and individual mandibles. Contour disparities were then represented using 3D overlays and heatmaps. Statistical analyses were performed using unpaired student t testing or Wilcoxon signed rank testing with 95% confidence interval as deemed appropriate by population-level normality assessment. RESULTS: Ninety-eight patients (53 females, 45 males) were included. Male mandibles showed greater bigonial width, intercondylar width, ramus height, and body length [p<0.005]. There was no statistically significant difference in the gonial angle measurements [p=0.62]. All relevant manual individual measurements demonstrated excellent concordance to their SSM counterparts. The 3D overlays of SSMs revealed squarer male chins with more lateral but less anterior projection than their female counterparts. Also, the female mandibles showed smoother transition at the gonial angle. CONCLUSIONS: SSM provides a novel tool to objectively evaluate volumetric and contour dimorphisms between genders. Moreover, this method can be automated, allowing for expedited comparisons between populations of interest compared to manual assessment. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 . Bullet points about the importance of this work: Advancing Anthropometric Assessment: Statistical shape modeling (SSM) offers a cutting-edge approach to visualizing gender-specific skeletal anatomic differences for aesthetic and gender-affirming facial surgery. Expediting Comparative Analysis: The workflow established in this paper streamlines the evaluative process, enabling rapid morphologic comparisons between populations. Patient-Centered Care: This study establishes a foundation for the development of SSMs in individualized operative planning.

Demographics, Utilization, Workflow, and Outcomes Based on Observational Data From the RSNA-ACR 3D Printing Registry.

PURPOSE: The aim of this study was to report data from the first 3 years of operation of the RSNA-ACR 3D Printing Registry. METHODS: Data from June 2020 to June 2023 were extracted, including demographics, indications, workflow, and user assessments. Clinical indications were stratified by 12 organ systems. Imaging modalities, printing technologies, and numbers of parts per case were assessed. Effort data were analyzed, dividing staff members into provider and nonprovider categories. The opinions of clinical users were evaluated using a Likert scale questionnaire, and estimates of procedure time saved were collected. RESULTS: A total of 20 sites and 2,637 cases were included, consisting of 1,863 anatomic models and 774 anatomic guides. Mean patient ages for models and guides were 42.4 ± 24.5 years and 56.3 ± 18.5 years, respectively. Cardiac models were the most common type of model (27.2%), and neurologic guides were the most common type of guide (42.4%). Material jetting, vat photopolymerization, and material extrusion were the most common printing technologies used overall (85.6% of all cases). On average, providers spent 92.4 min and nonproviders spent 335.0 min per case. Providers spent most time on consultation (33.6 min), while nonproviders focused most on segmentation (148.0 min). Confidence in treatment plans increased after using 3-D printing (P < .001). Estimated procedure time savings for 155 cases was 40.5 ± 26.1 min. CONCLUSIONS: Three-dimensional printing is performed at health care facilities for many clinical indications. The registry provides insight into the technologies and workflows used to create anatomic models and guides, and the data show clinical benefits from 3-D printing.

Utility of 3D-Printed Models in the Surgical Planning for Primary Spine Tumors: A Survey of International Spinal Oncology Experts.

STUDY DESIGN: Survey study. OBJECTIVES: The purpose of this study was to characterize the utility of 3D printed patient specific anatomic models for the planning of complex primary spine tumor surgeries. METHODS: A survey of individual members of an international study group of spinal oncology surgeons was performed. Participants were provided a clinical vignette, pathologic diagnosis, and pre-operative imaging for three primary spinal oncology cases. Study participants provided a free text surgical plan for resection and were then presented an associated 3D printed model for each case and asked to re-evaluate their surgical plan. RESULTS: Ten spinal oncology surgeons participated in the study, representing nine institutions across five countries. Four of the surgeons (40%) made significant changes to their surgical plan after reviewing the 3D models, including sacrifice of an additional nerve root to obtain negative margins, sparing an SI joint that was originally planned for inclusion in the en bloc resection, adjusting the location of osteotomy cuts, changes to the number of surgical stages and/or staging order, and preservation of neurology that was originally planned for sacrifice. The overall impression of the 3D models was positive, with 90% of the participants stating they found the 3D model useful in developing a surgical plan. CONCLUSIONS: Surgical planning for resection of primary spinal column tumors is challenging and time intensive. 3D printed patient specific surgical models may be an additional tool that can augment surgical planning and execution by improving the chance of accomplishing surgical resection goals and minimizing morbidity.

Minibeam Radiation Therapy Treatment (MBRT): Commissioning and First Clinical Implementation.

PURPOSE: Minibeam radiation therapy (MBRT) is characterized by the delivery of submillimeter-wide regions of high "peak" and low "valley" doses throughout a tumor. Preclinical studies have long shown the promise of this technique, and we report here the first clinical implementation of MBRT. METHODS AND MATERIALS: A clinical orthovoltage unit was commissioned for MBRT patient treatments using 3-, 4-, 5-, 8-, and 10-cm diameter cones. The 180 kVp output was spatially separated into minibeams using a tungsten collimator with 0.5 mm wide slits spaced 1.1 mm on center. Percentage depth dose (PDD) measurements were obtained using film dosimetry and plastic water for both peak and valley doses. PDDs were measured on the central axis for offsets of 0, 0.5, and 1 cm. The peak-to-valley ratio was calculated at each depth for all cones and offsets. To mitigate the effects of patient motion on delivered dose, patient-specific 3-dimensional-printed collimator holders were created. These conformed to the unique anatomy of each patient and affixed the tungsten collimator directly to the body. Two patients were treated with MBRT; both received 2 fractions. RESULTS: Peak PDDs decreased gradually with depth. Valley PDDs initially increased slightly with depth, then decreased gradually beyond 2 cm. The peak-to-valley ratios were highest at the surface for smaller cone sizes and offsets. In vivo film dosimetry confirmed a distinct delineation of peak and valley doses in both patients treated with MBRT with no dose blurring. Both patients experienced prompt improvement in symptoms and tumor response. CONCLUSIONS: We report commissioning results, treatment processes, and the first 2 patients treated with MBRT using a clinical orthovoltage unit. While demonstrating the feasibility of this approach is a crucial first step toward wider translation, clinical trials are needed to further establish safety and efficacy.

Creation and Validation of a Novel 3-Dimensional Pediatric Hip Ultrasound Model.

OBJECTIVES: The aim of this study was to create and validate a 3-dimensional (3D) ultrasound model with normal and abnormal pediatric hip joint anatomy that is comparable to a pediatric hip joint in appearance and anatomy and replicates sonographic characteristics of a pediatric hip joint. METHODS: A 3D rendering of the bone and soft tissue was created from a computed tomography pelvic scan of a pediatric patient. This rendering was modified to include a unilateral joint effusion. The bone was 3D printed with a photopolymer plastic, whereas the soft tissue was cast with a silicone mixture in a 3D-printed mold. The effusion was simulated by injecting saline into the soft tissue cavity surrounding the bone. The ultrasound model was validated by pediatric point-of-care ultrasonographers at an international pediatric ultrasound conference. RESULTS: A pediatric hip ultrasound model was developed that simulates both normal and abnormal pediatric hip joint anatomy, each with an appropriately sized, measurable joint effusion. Validation by pediatric point-of-care ultrasonographers showed that the key aspects of a normal pediatric hip joint (femoral physis, sloped femoral neck, and adequate soft tissue) with an identifiable and measurable effusion were included in the ultrasound model. CONCLUSIONS: In this study, we successfully created a cost-effective, reusable, and reproducible 3D pediatric hip ultrasound model. The majority of pediatric point-of-care ultrasonographers who evaluated the model agreed that this model is comparable to a pediatric patient for the purpose of teaching ultrasound skills and joint space measurement.

Patient-specific Implants Improve Volumetric Surgical Accuracy Compared to Stock Reconstruction Plates in Modern Paradigm Virtual Surgical Planning of Fibular Free Flaps for Head and Neck Reconstruction.

BACKGROUND: Virtual surgical planning (VSP) for composite microvascular free flaps has become standard of care for oncologic head and neck reconstruction. Controversy remains as to the use of three-dimensional (3D)-printed patient-specific titanium implants (PSIs) versus hand-bent stock reconstruction plates. Proponents of PSIs cite improved surgical accuracy, reduced operative times, and improved clinical outcomes. Detractors purport increased cost associated with PSIs and presumed equivalent accuracy with less expensive stock plates. PURPOSE: The study purpose was to measure and compare the 3D-volumetric accuracy of PSI versus stock reconstruction plates among subjects undergoing VSP-guided mandibular fibular free flap reconstruction. STUDY DESIGN, SETTING, SAMPLE: A retrospective cohort study of subjects undergoing VSP-guided fibular free flap reconstructions at Mayo Clinic between 2016 and 2023 was performed. Subjects were excluded for non-VSP guidance, midfacial reconstruction, nonfibular free flaps, and lack of requisite study variables. PREDICTOR VARIABLE: The primary predictor was the type of reconstruction plate utilized (PSI vs stock plate). MAIN OUTCOME VARIABLE: The main outcome was volumetric surgical accuracy of the final reconstruction compared to the preoperative surgical plan by root mean square error (RMSE) calculation. Lower RMSE values indicated a higher surgical accuracy. COVARIATES: Covariates included age, sex, race, smoking status, American Society of Anesthesiologists (ASA) Physical Status Classification System, Charlson Comorbidity Index, preoperative diagnosis, and number of fibular segments. ANALYSES: Differences in surgical accuracy were assessed between preoperative and postoperative segmented scans using volumetric overlays from which RMSE values were calculated. Univariate and multivariate modeling of plate type to RMSE calculation was performed. Statistical significance set to P < .05. RESULTS: Total of 130 subjects were identified, 105 PSI and 25 stock plates. Calculated mean RMSE in millimeters (mm) for stock plates was 1.46 (standard deviation: 0.33) and 1.15 (standard deviation: 0.36) for PSIs. Univariate modeling demonstrated a statistically significant difference in RMSE of 0.31 (95% confidence interval: 0.16-0.47) (P < .001) equating to a 21.2% (P < .001) improved volumetric surgical accuracy for PSIs. The association of improved volumetric accuracy with PSIs has been maintained in all multivariate models controlling for confounding. CONCLUSION AND RELEVANCE: In modern era VSP-guided head and neck fibular free flap reconstruction, patient-specific 3D-printed titanium implants confer a statistically significant improvement in volumetric surgical accuracy over stock reconstruction plates.

Photogrammetry scans for neuroanatomy education - a new multi-camera system: technical note.

Photogrammetry scans has directed attention to the development of advanced camera systems to improve the creation of three-dimensional (3D) models, especially for educational and medical-related purposes. This could be a potential cost-effective method for neuroanatomy education, especially when access to laboratory-based learning is limited. The aim of this study was to describe a new photogrammetry system based on a 5 Digital Single-Lens Reflex (DSLR) cameras setup to optimize accuracy of neuroanatomical 3D models. One formalin-fixed brain and specimen and one dry skull were used for dissections and scanning using the photogrammetry technique. After each dissection, the specimens were placed inside a new MedCreator® scanner (MedReality, Thyng, Chicago, IL) to be scanned with the final 3D model being displayed on SketchFab® (Epic, Cary, NC) and MedReality® platforms. The scanner consisted of 5 cameras arranged vertically facing the specimen, which was positioned on a platform in the center of the scanner. The new multi-camera system contains automated software packages, which allowed for quick rendering and creation of a high-quality 3D models. Following uploading the 3D models to the SketchFab® and MedReality® platforms for display, the models can be freely manipulated in various angles and magnifications in any devices free of charge for users. Therefore, photogrammetry scans with this new multi-camera system have the potential to enhance the accuracy and resolution of the 3D models, along with shortening creation time of the models. This system can serve as an important tool to optimize neuroanatomy education and ultimately, improve patient outcomes.

Extraocular muscle electromyographic recordings for intraoperative monitoring of cranial nerves III, IV, and VI: a single-center experience with intraorbital electrodes.

OBJECTIVE: The objective of this study was to describe the quantitative features of intraoperative electromyographic recordings obtained from cranial nerve III, IV, and VI neuromonitoring using 25-mm intraorbital electrodes, in the larger context of demonstrating the practicality of this technique during neurosurgical cases. METHODS: A 25-mm-long shaft-insulated intraorbital needle electrode is routinely used at the authors' institution for extraocular muscle (EOM) electromyographic monitoring of the inferior rectus, superior oblique, and/or lateral rectus muscles when their function is at risk. Cases monitored between January 1, 2021, and December 31, 2022, were reviewed for patient demographics, tumor location and pathology, EOMs monitored, pre- and postoperative examination, and complications from electrode placement. Compound muscle action potentials on triggered electromyography, as well as neurotonic discharges on free-run electromyography, were described quantitatively. RESULTS: There were 141 cases in 139 patients reviewed during the 24-month time span, with 278 EOMs monitored (inferior rectus/superior oblique/lateral rectus muscles 68/68/142). Triggered electromyography yielded biphasic or triphasic compound muscle action potentials from EOMs with a mean onset latency of 1.51 msec (range 0.94-3.22 msec), mean maximal peak-to-trough amplitude of 1073.93 µV (range 76.75-7796.29 µV), and high specificity for the channel in nearly all cases. Neurotonic discharges were recorded in 30 of the 278 EOMs (with all 3 muscles represented) and associated with a greater incidence of new or worsened ophthalmoparesis (OR 4.62, 95% CI 1.3-16.4). There were 2 cases of small periorbital ecchymosis attributed to needle placement; additionally, 1 case of needle-related intraorbital hematoma occurred after the review period. CONCLUSIONS: The 25-mm shaft-insulated intraorbital electrode facilitates robust and consistent electromyographic recordings of EOMs that are advantageous over existing techniques. Combined with the relative ease of needle placement and low rate of complications, the technique is practical for neuromonitoring during craniotomies.

Inhibition of CERS1 in skeletal muscle exacerbates age-related muscle dysfunction.

Age-related muscle wasting and dysfunction render the elderly population vulnerable and incapacitated, while underlying mechanisms are poorly understood. Here, we implicate the CERS1 enzyme of the de novo sphingolipid synthesis pathway in the pathogenesis of age-related skeletal muscle impairment. In humans, CERS1 abundance declines with aging in skeletal muscle cells and, correlates with biological pathways involved in muscle function and myogenesis. Furthermore, CERS1 is upregulated during myogenic differentiation. Pharmacological or genetic inhibition of CERS1 in aged mice blunts myogenesis and deteriorates aged skeletal muscle mass and function, which is associated with the occurrence of morphological features typical of inflammation and fibrosis. Ablation of the CERS1 orthologue lagr-1 in Caenorhabditis elegans similarly exacerbates the age-associated decline in muscle function and integrity. We discover genetic variants reducing CERS1 expression in human skeletal muscle and Mendelian randomization analysis in the UK biobank cohort shows that these variants reduce muscle grip strength and overall health. In summary, our findings link age-related impairments in muscle function to a reduction in CERS1, thereby underlining the importance of the sphingolipid biosynthesis pathway in age-related muscle homeostasis.

Assessment of minimum target dose as a predictor of local failure after spine SBRT.

OBJECTIVES: Metastasis-directed stereotactic body radiation therapy (SBRT) has demonstrated robust clinical benefits in carefully selected patients, improving local control and even overall survival (OS). We assess a large database to determine clinical and dosimetric predictors of local failure after spine SBRT. METHODS: Spine SBRT treatments with imaging follow-up were identified. Patients were treated with a simultaneous integrated boost technique using 1 or 3 fractions, delivering 20-24 Gy in 1 fraction to the gross tumor volume (GTV) and 16 Gy to the low dose volume (or 27-36 Gy and 21-24 Gy for 3 fraction treatments). Exclusions included: lack of imaging follow-up, proton therapy, and benign primary histologies. RESULTS: 522 eligible spine SBRT treatments (68 % single fraction) were identified in 377 unique patients. Patients had a median OS of 43.7 months (95 % confidence interval: 34.3-54.4). The cumulative incidence of local failure was 10.5 % (7.4-13.4) at 1 year and 16.3 % (12.6-19.9) at 2 years. Local control was maximized at 15.3 Gy minimum dose for single-fraction treatment (HR = 0.31, 95 % CI: 0.17 - 0.56, p < 0.0001) and confirmed via multivariable analyses. Cumulative incidence of local failure was 6.1 % (2.6-9.4) vs. 14.2 % (8.3-19.8) at 1 year using this cut-off, with comparable findings for minimum 14 Gy. Additionally, epidural and soft tissue involvement were predictive of local failure (HR = 1.77 and 2.30). CONCLUSIONS: Spine SBRT offers favorable local control; however, minimum dose to the GTV has a strong association with local control. Achieving GTV minimum dose of 14-15.3 Gy with single fraction SBRT is recommended whenever possible.

MR Lymphangiography in Lymphatic Disorders: Clinical Applications, Institutional Experience, and Practice Development.

Lymphatic flow and anatomy can be challenging to study, owing to variable lymphatic anatomy in patients with diverse primary or secondary lymphatic pathologic conditions and the fact that lymphatic imaging is rarely performed in healthy individuals. The primary components of the lymphatic system outside the head and neck are the peripheral, retroperitoneal, mesenteric, hepatic, and pulmonary lymphatic systems and the thoracic duct. Multiple techniques have been developed for imaging components of the lymphatic system over the past century, with trade-offs in spatial, temporal, and contrast resolution; invasiveness; exposure to ionizing radiation; and the ability to obtain information on dynamic lymphatic flow. More recently, dynamic contrast-enhanced (DCE) MR lymphangiography (MRL) has emerged as a valuable tool for imaging both lymphatic flow and anatomy in a variety of congenital and acquired primary or secondary lymphatic disorders. The authors provide a brief overview of lymphatic physiology, anatomy, and imaging techniques. Next, an overview of DCE MRL and the development of an MRL practice and workflow in a hybrid interventional MRI suite incorporating cart-based in-room US is provided, with an emphasis on multidisciplinary collaboration. The spectrum of congenital and acquired lymphatic disorders encountered early in an MRL practice is provided, with emphasis on the diversity of imaging findings and how DCE MRL can aid in diagnosis and treatment of these patients. Methods such as DCE MRL for assessing the hepatic and mesenteric lymphatic systems and emerging technologies that may further expand DCE MRL use such as three-dimensional printing are introduced. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.